title: Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes.
abstract: Toxicological characterization of manufactured nanomaterials (NMs) is essential for safety assessment, while keeping pace with innovation from their development and application in consumer products. The specific physicochemical properties of NMs, including size and morphology, might influence their toxicity and have impact on human health. The present work aimed to evaluate the genotoxicity of nanosized titanium dioxide (TiO2), synthetic amorphous silica (SAS) and multiwalled carbon nanotubes (MWCNTs), in human lymphocytes. The morphology and size of those NMs were characterized by transmission electron microscopy, while the hydrodynamic particle size-distributions were determined by dynamic light scattering. Using a standardized procedure to ensure the dispersion of the NMs and the cytokinesis-block micronucleus assay (without metabolic activation), we observed significant increases in the frequencies of micronucleated binucleated cells (MNBCs) for some TiO2 NMs and for two MWCNTs, although no clear dose-response relationships could be disclosed. In contrast, all forms of SAS analyzed in this study were unable to induce micronuclei. The present findings increase the weight of evidence towards a genotoxic effect of some forms of TiO2 and some MWCNTs. Regarding safety assessment, the differential genotoxicity observed for closely related NMs highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NMs.
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Tavares
authors.forename: Henriqueta
authors.initials: H
authors.lastname: Louro
authors.forename: Susana
authors.initials: S
authors.lastname: Antunes
authors.forename: Stephanie
authors.initials: S
authors.lastname: Quarré
authors.forename: Sophie
authors.initials: S
authors.lastname: Simar
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: De Temmerman
authors.forename: Eveline
authors.initials: E
authors.lastname: Verleysen
authors.forename: Jan
authors.initials: J
authors.lastname: Mast
authors.forename: Keld A
authors.initials: KA
authors.lastname: Jensen
authors.forename: Hannu
authors.initials: H
authors.lastname: Norppa
authors.forename: Fabrice
authors.initials: F
authors.lastname: Nesslany
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Silva
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008027:Light; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests; D046529:Microscopy, Electron, Transmission; D009152:Mutagenicity Tests / Q000379:methods*; D049329:Nanostructures / Q000633:toxicity; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D012542:Scattering, Radiation; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D037742:Nanotubes, Carbon; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium
keywords: Micronucleus assay; Morphology and size; Multiwalled carbon nanotubes; Primary human lymphocytes; Synthetic amorphous silica nanomaterials; Titanium dioxide nanomaterials